Effective treatment for neurodegenerative diseases, such as (without limitation) Alzheimer's, Parkinson's, and Lou Gehrig's disease is still lacking. For example, it has been recently reported that Alzheimer's disease is the seventh leading cause of death in the United States. It has also been reported that 26 million people worldwide, including 5 million Americans, have Alzheimer's disease. Only marginal symptomatologic treatment is available to date. Statistics and projections indicate that 1 in 2 subjects above the age of 80 experience some level of clinically relevant cognitive impairment and with the projections indicating an increase of the average lifespan of the humans the burden deriving to society will be immense.
There are several indications that the NF-kB pathway plays a role in neuronal resilience and in the changes induced by cellular learning such as long term potentiation and depression. Several reports have shown that knocking out NF-kB activity in the brain causes sensitization to toxic stimuli, such as β-amyloid, excitatory aminoacids and to trauma. Also NF-kB activation has been involved in long term potentiation and depression the cellular correlates of learning and memory. In addition, activation of NF-kB is a known anti-apoptosis mechanism. Failure of NF-kB in other systems can also be counteracted by compounds of this disclosure and therefore will be covered by this disclosure.